In young and old mice exposed to 500 R, the rate of regeneration of immune competence is inversely related to the self renewal activity of CFU-S; i.e., old mice with an inferior regenerative capacity possessed stem cells with a rapid self renewing capacity, whereas young mice with a superior regenerative capacity possessed stem cells with a slow self renewing capacity. These results suggest that the decrease in the ability of old mice to regenerate their immunologic activities after exposure to 500 R may be due in part to the inability of their stem cells to differentiate into immunocompetence cells as efficiently as in young mice, perhaps because aging has altered the self renewal-differentiation balance of stem cells in favor of self renewal. The immune system of old mice is vulnerable to stress because stem cells favor self renewal over differentiation when they are stressed. Evaluation of three ways aging could alter the self renewal-differentiation pattern of stem cells form the objectives of this proposal. They are: (1) to determine whether the cellular milieu is responsible for age-related change in the number and self renewal activity of precursor T stem cells. (2) To determine whether bone marrow stromal cells can alter the number and self renewal activity of precursor T stem cells; and (3) to determine whether thymic tissue is responsible for age-related change in the number and self renewal activity of precursor T stem cells. The self renewal activity of stem cells will be assessed by replicate plating of post T and pre T stem cells in vitro and CFU-S in vivo. The results of these studies are expected to provide information on how aging alters the mechanism regulating the self renewal and differentation activities of stem cells of the lymphohematopoietic system by subjecting the system to stress. The knowledge would be helpful to radiation therapists treating elderly patients and to clinicians treating patients with stressful disease of the lymphohematopoietic system.